Suppression of p160ROCK bypasses cell cycle arrest after Aurora-A/STK15 depletion

Du, J., Hannon, G. J. (June 2004) Suppression of p160ROCK bypasses cell cycle arrest after Aurora-A/STK15 depletion. Proc Natl Acad Sci U S A, 101 (24). pp. 8975-80. ISSN 0027-8424 (Print)

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DOI: 10.1073/pnas.0308484101


Alterations in the expression and activity of the centrosomal kinase, Aurora-A/serine/threonine kinase 15 (STK15), affect genomic stability, disrupt the fidelity of centrosome duplication, and induce cellular transformation. Here, we provide evidence that p160ROCK, a Rho-associate serine/threonine kinase, associates with Aurora-A in a protein complex with other STK15-associated factors. Suppression of Aurora-A by small interfering RNA in HeLa cells blocks the ability of centrosomes to organize normal mitotic spindles, induces G(2)/M cell cycle arrest, and promotes accumulation of tetraploid cells. In many cases, one outcome of such abnormalities is apoptosis. Introduction of a second genetic lesion, suppression of p160ROCK by RNA interference, can rescue abnormal mitotic spindle formation, release the G(2)/M cell cycle arrest, and alleviate apoptosis, leading to a greater accumulation of aneuploid cells. These results suggest that Aurora-A and p160ROCK act in a common genetic pathway that promotes and monitors progression through G(2)/M.

Item Type: Paper
Uncontrolled Keywords: Apoptosis physiology Cell Cycle physiology Cells Cultured Chromosomes ultrastructure Fibroblasts metabolism Fluorescent Antibody Technique G2 Phase physiology Gene Silencing Genomic Instability physiology Hela Cells Humans Intracellular Signaling Peptides and Proteins Mitosis physiology Mitotic Spindle Apparatus ultrastructure Protein-Serine-Threonine Kinases chemistry deficiency genetics metabolism RNA Small Interfering pharmacology Transfection
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: CSHL Librarian
Date: 15 June 2004
Date Deposited: 03 Feb 2012 16:05
Last Modified: 09 Nov 2017 17:07
PMCID: PMC428457
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